NM_004937.3(CTNS):c.681G>A (p.Glu227=) AND Nephropathic cystinosis

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Sep 25, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000668750.12

Allele description [Variation Report for NM_004937.3(CTNS):c.681G>A (p.Glu227=)]

NM_004937.3(CTNS):c.681G>A (p.Glu227=)

Genes:

CTNS-AS1:CTNS antisense RNA 1 [Gene - HGNC]
CTNS:cystinosin, lysosomal cystine transporter [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_004937.3(CTNS):c.681G>A (p.Glu227=)

Other names:

p.Glu227=

HGVS:

NC_000017.11:g.3656795G>A
NG_012489.2:g.25328G>A
NM_001031681.3:c.681G>A
NM_001374492.1:c.681G>A
NM_001374493.1:c.240G>A
NM_001374494.1:c.240G>A
NM_001374495.1:c.240G>A
NM_001374496.1:c.240G>A
NM_004937.3:c.681G>AMANE SELECT
NP_001026851.2:p.Glu227=
NP_001361421.1:p.Glu227=
NP_001361422.1:p.Glu80=
NP_001361423.1:p.Glu80=
NP_001361424.1:p.Glu80=
NP_001361425.1:p.Glu80=
NP_004928.2:p.Glu227=
NC_000017.10:g.3560089G>A
NM_004937.2:c.681G>A

Links:

dbSNP: rs778414542

NCBI 1000 Genomes Browser:

rs778414542

Molecular consequence:

NM_001031681.3:c.681G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001374492.1:c.681G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001374493.1:c.240G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001374494.1:c.240G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001374495.1:c.240G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001374496.1:c.240G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_004937.3:c.681G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Nephropathic cystinosis (CTNS)
Synonyms:: Lysosomal cystine transport protein, defect of; Cystinosin, defect of; Abderhalden Lignac Kaufmann disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100151; MedGen: C2931187; Orphanet: 213; Orphanet: 411629; OMIM: 219800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793400	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Pathogenic (Aug 15, 2017)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12442267, 21786142, 19852576, 23640116 Citation Link,
SCV003841997	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23640116, 19852576, 25741868
SCV004031449	Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 4, 2023)	inherited	clinical testing
SCV004212946	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 25, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Turkish	inherited	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.

Kalatzis V, Cohen-Solal L, Cordier B, Frishberg Y, Kemper M, Nuutinen EM, Legrand E, Cochat P, Antignac C.

Hum Mutat. 2002 Dec;20(6):439-46.

PubMed [citation]

PMID:: 12442267

Genetic basis of cystinosis in Turkish patients: a single-center experience.

Topaloglu R, Vilboux T, Coskun T, Ozaltin F, Tinloy B, Gunay-Aygun M, Bakkaloglu A, Besbas N, van den Heuvel L, Kleta R, Gahl WA.

Pediatr Nephrol. 2012 Jan;27(1):115-21. doi: 10.1007/s00467-011-1942-6. Epub 2011 Jul 24.

PubMed [citation]

PMID:: 21786142
PMCID:: PMC3501933

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000793400.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV003841997.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Functional studies provide supporting evidence of the variant having a damaging effect on the gene or gene product (PMID: 19852576). In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 0.80). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 23640116 / 19852576‚Äö21786142). The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000553330). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, SCV004031449.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Turkish	not provided	not provided	not provided	clinical testing	not provided

Description

missense variant type:snv

Description

In-Silico PredictorsPP3: Pathogenic Strong

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004212946.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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